tbuckley/cabot-search huggingface dataset:
Radiomics to evaluate interlesion heterogeneity and to predict lesion response and patient outcomes using a validated signature of CD8 cells in advanced melanoma patients treated with anti-PD1 immunotherapy
Authors: Roger Sun, Marvin Lerousseau, Jade Briend-Diop, Emilie Routier, Severine Roy, Théophraste Henry, Kanta Ka, Rui Jiang, Nawal Temar, Alexandre Carré, Adrien Laville, Anthony Hamaoui, Pierre-Antoine Laurent, Angela Rouyar, Charlotte Robert, Caroline Robert, Eric Deutsch
Journal: Journal for ImmunoTherapy of Cancer (2022)

While there is still a significant need to identify potential biomarkers that can predict which patients are most likely to respond to immunotherapy treatments, radiomic approaches have shown promising results. The objectives of this study were to evaluate whether a previously validated radiomics signature of CD8 T-cells could predict progressions at a lesion level and whether the spatial heterogeneity of this radiomics score could be used at a patient level to assess the clinical response and survival of melanoma patients.Clinical data from patients with advanced melanoma treated in our center with immunotherapy were retrieved. Radiomic features were extracted and the CD8 radiomics signature was applied. A progressive lesion was defined by an increase in lesion size of 20% or more. Dispersion metrics of the radiomics signature were estimated to evaluate the impact of interlesion heterogeneity on patient's response. Fine-tuned cut-offs for predicting overall survival were evaluated after splitting data into training and test sets.A total of 136 patients were included in this study, with 1120 segmented lesions at baseline, and 1052 lesions at first evaluation. A low CD8 radiomics score at baseline was associated with a significantly higher risk of lesion progression (AUC=0.55, p=0.0091), especially for lesions larger than &gt;1 mL (AUC=0.59 overall, p=0.0035, with AUC=0.75, p=0.002 for subcutaneous lesions, AUC=0.68, p=0.01, for liver lesions and AUC=0.62, p=0.03 for nodes). The least infiltrated lesion according to the radiomics score of CD8 T-cells was positively associated with overall survival (training set HR=0.31, p=0.00062, test set HR=0.28, p=0.016), which remained significant in a multivariate analysis including clinical and biological variables.These results confirm the predictive value at a lesion level of the biologically inspired CD8 radiomics score in melanoma patients treated with anti-PD1-based immunotherapy and may be interesting to assess the disease spatial heterogeneity to evaluate the patient prognosis with potential clinical implication such as tumor selection for focal ablative therapies.
Tumoral melanosis mimicking residual melanoma in the setting of talimogene laherparepvec treatment
Authors: Song Y Park, Austin R Green, Rouba Hadi, Coley Doolittle-Amieva, Jennifer Gardner, Ata S Moshiri
Journal: Journal for ImmunoTherapy of Cancer (2022)

Talimogene laherparepvec (T-VEC) has become an increasingly popular treatment option for surgically non-resectable, recurrent melanoma, usually of cutaneous metastases. The complete response (CR) rate has been reported to be ~20% with a median of ~9 months to achieve it. In real-world practice, decrease of tumor size often occurs rapidly within the first 2–3 months, while improvement of the pigmentation takes several more months. Such clinical observation of lasting pigmentation could be explained by tumorous melanosis—a histopathological term referring to the presence of a melanophage-rich inflammatory infiltrate without remaining viable tumor cells. Herein, we report six patients with metastatic cutaneous melanoma who were treated with T-VEC. Biopsies were performed after observing clinical responses in the injected tumors. Pathological evaluation demonstrated non-viable or absent tumor tissue with tumorous melanosis in all cases. To accurately assess response to therapy and potentially decrease unnecessary additional T-VEC treatments, serial biopsy of ‘stable’ lesions should be considered to assess the presence or absence of viable tumor.
Long-lived plasma cells accumulate in the bone marrow at a constant rate from early in an immune response
Authors: Marcus James Robinson, Mark R. Dowling, Catherine Pitt, Kristy O’Donnell, Rosela H. Webster, Danika L. Hill, Zhoujie Ding, Alexandra R. Dvorscek, Erica J. Brodie, Philip D. Hodgkin, Isaak Quast, David Mathew Tarlinton
Journal: Science Immunology (2022)

Vaccines work largely by generating long-lived plasma cells (LLPCs), but knowledge of how such cells are recruited is sparse. Although it is clear that LLPCs preferentially originate in germinal centers (GCs) and relocate to survival niches in bone marrow where they can persist for decades, the issues of the timing of LLPC recruitment and the basis of their retention remain uncertain. Here, using a genetic timestamping system in mice, we show that persistent PCs accrue in bone marrow at an approximately constant rate of one cell per hour over a period spanning several weeks after a single immunization with a model antigen. Affinity-based selection was evident in persisting PCs, reflecting a relative and dynamic rather than absolute affinity threshold as evidenced by the changing pattern of V H gene somatic mutations conveying increased affinity for antigen. We conclude that the life span of persistent, antigen-specific PCs is in part intrinsic, preprogrammed, and varied and that their final number is related to the duration of the response in a predictable way. This implies that modulating vaccines to extend the duration of the GC reaction will enhance antibody-mediated protective immunity.
Irritable bowel syndrome: treatment based on pathophysiology and biomarkers
Authors: Michael Camilleri, Guy Boeckxstaens
Journal: Gut (2022)

Objective To appraise the evidence that pathophysiological mechanisms and individualised treatment directed at those mechanisms provide an alternative approach to the treatment of patients with irritable bowel syndrome (IBS). Design A PubMED-based literature review of mechanisms and treatment of IBS was conducted independently by the two authors, and any differences of perspective or interpretation of the literature were resolved following discussion. Results The availability of several noninvasive clinical tests can appraise the mechanisms responsible for symptom generation in IBS, including rectal evacuation disorders, abnormal transit, visceral hypersensitivity or hypervigilance, bile acid diarrhoea, sugar intolerances, barrier dysfunction, the microbiome, immune activation and chemicals released by the latter mechanism. The basic molecular mechanisms contributing to these pathophysiologies are increasingly recognised, offering opportunities to intervene with medications directed specifically to food components, receptors and potentially the microbiome. Although the evidence supporting interventions for each mechanism is not at the same level of proof, the current state-of-the-art provides the opportunity to advance the practice from treatment based on symptoms to individualisation of treatment guided by pathophysiology and clinically identified biomarkers. Conclusion These advances augur well for the implementation of evidence-based individualised treatment for patients with IBS based on actionable biomarkers or psychological disturbances.
Risk of cervical precancer among HPV–negative women in the Netherlands and its association with previous HPV and cytology results: A follow-up analysis of a randomized screening study
Authors: Federica Inturrisi, Lawrence Rozendaal, Nienke J. Veldhuijzen, Daniëlle A. M. Heideman, Chris J. L. M. Meijer, Johannes Berkhof
Journal: PLoS Medicine (2022)

Background Human papillomavirus (HPV)-based screening programs still use one-size-fits-all protocols but efficiency and efficacy of programs may be improved by stratifying women based on previous screening results. Methods and findings We studied the association between cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and previous screening results in the Population-Based Screening Study Amsterdam (POBASCAM) trial, performed in the Netherlands in the setting of regular screening, where women aged from 29 to 61 years old were invited to cytology and HPV co-testing at enrolment in year 1999/2002 and at the next round in 2003/2007. We selected 18,448 women (9,293 from the intervention group and 9,155 from the control group) who tested HPV–negative in 2003/2007 and did not have cervical intraepithelial neoplasia grade 2 or worse (CIN2+) or hysterectomy after enrolment. Follow-up was collected until 14 years after the 2003/2007 screen, covering 4 rounds of screening. Risk of CIN3+ and CIN2+ among women with an HPV–negative test, irrespective of previous round results and stratified according to previous round HPV and cytology results, were calculated by the Kaplan–Meier method. During 14 years of follow-up, 62 CIN3+ cases (24 in the intervention group and 38 in the control group) were detected. HPV–negative women had a 14-year CIN3+ risk of 0.48% (95% confidence interval 0.37 to 0.62) and CIN2+ risk of 1.17% (0.99 to 1.38). The CIN3+ risk among HPV–negative women was increased in women with a previous positive HPV test (2.36%, 1.20 to 4.63; p &lt; 0.001) or co-test (1.68%, 0.87 to 3.20; p &lt; 0.001) and, equivalently, decreased in women with a previous negative HPV test (0.43%, 0.33 to 0.57) or a negative co-test (0.43%, 0.33 to 0.57). The CIN3+ risk was not influenced by the previous cytology result. The CIN3+ risk among HPV–negative women was increased after both a previous HPV16–positive test (3.90%, 1.47 to 10.12; p &lt; 0.001) and a previous HPV16–negative/HPVother–positive test (1.91%, 0.76 to 4.74; p = 0.002). For endpoint CIN2+ (147 cases), findings were similar except that the CIN2+ risk was increased after previous abnormal cytology (4.06%, 2.30 to 7.12; p &lt; 0.001). The presented risk estimates were calculated by tracking histological results through the Dutch nationwide pathology archive (PALGA) and were not adjusted for non-compliance with the colposcopy referral advice. Conclusions HPV–negative women had an increased long-term risk of CIN3+ when the HPV test in the previous screening round was positive. This supports the implementation of risk-based intervals that depend on HPV results in the current and previous screening round. Trial registration POBASCAM trial, trial registration number ISRCTN20781131 .
Rates of repeated colonoscopies to clean the colon from low-risk and high-risk adenomas: results from the EPoS trials
Authors: Frederik Emil Juul, Kjetil Garborg, Eugen Nesbakken, Magnus Løberg, Paulina Wieszczy, Joaquín Cubiella, Mette Kalager, Michael F Kaminski, Rune Erichsen, Hans-Olov Adami, Monika Ferlitsch, Siv K B Furholm, Ann G Zauber, Enrique Quintero, Marek Bugajski, Øyvind Holme, Evelien Dekker, Rodrigo Jover, Michael Bretthauer
Journal: Gut (2022)

Objective High-quality colonoscopy (adequate bowel preparation, whole-colon visualisation and removal of all neoplastic polyps) is a prerequisite to start polyp surveillance, and is ideally achieved in one colonoscopy. In a large multinational polyp surveillance trial, we aimed to investigate clinical practice variation in number of colonoscopies needed to enrol patients with low-risk and high-risk adenomas in polyp surveillance. Design We retrieved data of all patients with low-risk adenomas (one or two tubular adenomas &lt;10 mm with low-grade dysplasia) and high-risk adenomas (3–10 adenomas, ≥1 adenoma ≥10 mm, high-grade dysplasia or villous components) in the European Polyp Surveillance trials fulfilling certain logistic and methodologic criteria. We analysed variations in number of colonoscopies needed to achieve high-quality colonoscopy and enter polyp surveillance by endoscopy centre, and by endoscopists who enrolled ≥30 patients. Results The study comprised 15 581 patients from 38 endoscopy centres in five European countries; 6794 patients had low-risk and 8787 had high-risk adenomas. 961 patients (6.2%, 95% CI 5.8% to 6.6%) underwent two or more colonoscopies before surveillance began; 101 (1.5%, 95% CI 1.2% to 1.8%) in the low-risk group and 860 (9.8%, 95% CI 9.2% to 10.4%) in the high-risk group. Main reasons were poor bowel preparation (21.3%) or incomplete colonoscopy/polypectomy (14.4%) or planned second procedure (27.8%). Need of repeat colonoscopy varied between study centres ranging from 0% to 11.8% in low-risk adenoma patients and from 0% to 63.9% in high-risk adenoma patients. On the second colonoscopy, the two most common reasons for a repeat (third) colonoscopy were piecemeal resection (26.5%) and unspecified reason (23.9%). Conclusion There is considerable practice variation in the number of colonoscopies performed to achieve complete polyp removal, indicating need for targeted quality improvement to reduce patient burden. Trial registration number NCT02319928 .
Use of over-the-scope clip (OTSC) versus standard therapy for the prevention of rebleeding in large peptic ulcers (size ≥1.5 cm): an open-labelled, multicentre international randomised controlled trial
Authors: Shannon Chan, Rapat Pittayanon, Hsiu-Po Wang, Jiann-Hwa Chen, Anthony YB Teoh, Yu Ting Kuo, Raymond SY Tang, Hon Chi Yip, Stephen Ka Kei Ng, Sunny Wong, Joyce Wing Yan Mak, Heyson Chan, Louis Lau, Rashid N Lui, Marc Wong, Rungsun Rerknimitr, Enders K Ng, Philip Wai Yan Chiu
Journal: Gut (2022)

Introduction Over-the-scope clip (OTSC) has been used recently for primary haemostasis of peptic ulcers. This study aimed to compare the efficacy of OTSC to standard endoscopic therapy in primary treatment of patients with peptic ulcer bleeding that are of size ≥1.5 cm. The target population accounts for only 2.5% of all upper GI bleeders. Methods This was a multicentre international randomised controlled trial from July 2017 to October 2020. All patients with Forest IIa or above peptic ulcers of ≥1.5 cm were included. Primary outcome was 30-day clinical rebleeding. Secondary endpoints include 3-day all-cause mortality, transfusion requirement, hospital stay, technical and clinical success, and further interventions. 100 patients are needed to yield a power of 80% to detect a difference of −0.15 at the 0.05 significance level (alpha) using a two-sided Z-test (pooled). Results 100 patients were recruited. Success in achieving primary haemostasis was achieved in 46/50 (92%) and 48/50 (96%) in the OTSC and conventional arm, respectively. Among patients who had success in primary haemostasis, 2/46 (4.35%) patients in the OTSC arm and 9/48 (18.75%) patients in the conventional arm developed 30-day rebleeding (p=0.03). However, in an intention-to-treat analysis, there was no difference in rebleeding within 30 days (5/50 (10%) OTSC vs 9/50 (18%) standard, p=0.23) or all-cause mortality (2/50 (4%) OTSC vs 4/50 (8%) standard, p=0.68; OR=2.09, 95% CI 0.37 to 11.95). There was also no difference in transfusion requirement, hospital stay, intensive care unit admission and further interventions. Conclusion The routine use of OTSC as primary haemostasis in large bleeding peptic ulcers was not associated with a significant decrease in 30-day rebleeding. Trial registration number NCT03160911 .
<i>APC</i>mosaicism, not always isolated: two first-degree relatives with apparently distinct<i>APC</i>mosaicism
Authors: Diantha Terlouw, Frederik J Hes, Manon Suerink, Arnoud Boot, Alexandra M J Langers, Carli M Tops, Monique E van Leerdam, Christi J van Asperen, Steve G Rozen, Emilia K Bijlsma, Tom van Wezel, Hans Morreau, Maartje Nielsen
Journal: Gut (2022)
A Two-Step Frailty Assessment Strategy in Older Patients With Solid Tumors: A Decision Curve Analysis
Authors: Adolfo González Serrano, Marie Laurent, Thomas Barnay, Claudia Martínez-Tapia, Etienne Audureau, Pascaline Boudou-Rouquette, Thomas Aparicio, Florence Rollot-Trad, Pierre Soubeyran, Carine Bellera, Philippe Caillet, Elena Paillaud, Florence Canouï-Poitrine
Journal: Journal of Clinical Oncology (2022)

The intended clinical value of frailty screening is to identify unfit patients needing geriatric assessment (GA) and to prevent unnecessary GA in fit patients. These hypotheses rely on the sensitivity and specificity of screening tests, but they have not been verified.
Vacancy‐Modulated of CuS for Highly Antibacterial Efficiency via Photothermal/Photodynamic Synergetic Therapy
Authors: Zhihao Zhang, Jinghong Wen, Jie Zhang, Donggang Guo, Quanxi Zhang
Journal: Advanced Healthcare Materials (2022)

Cu-based nanomaterials have been developed to alleviate the problem of antibiotic resistance due to their superior properties and good biocompatibility. Defects in nanomaterials have a major role in improving photocatalytic performance. Herein, two CuS nanospheres with predominant VCuSCu and VCuSS vacancy (abbreviated as CuS and CuS-T150, respectively) characterized by positron annihilation spectra are synthesized. The combination of experimental and theoretical calculation results demonstrates that CuS-T150 exhibits excellent antibacterial, achieving bactericidal rates of 99.9% against to Escherichia coli (E. coli) under 808 nm laser irradiation. Compared with CuS, the superior antimicrobial activity of CuS-T150 is mainly attributed to its stronger ability to adsorb oxygen molecules, more easily bind with surface of E. coli, and higher photothermal conversion efficiency (PTCE). This work provides a deeper understanding of nanomaterials with vacancy modulated the antibacterial efficiency by synergistic effect of photodynamic and photothermal therapy.
Randomized Phase II Trial of Sunitinib or Cediranib in Alveolar Soft Part Sarcoma
Authors: James Nguyen, Naoko Takebe, Shivaani Kummar, Albiruni Razak, Sant P. Chawla, Suzanne George, Shreyaskumar R. Patel, Mary Louise Keohan, Sujana Movva, Geraldine O'Sullivan Coyne, Khanh Do, Lamin Juwara, Brooke Augustine, Seth M. Steinberg, Laura Kuhlmann, S. Percy Ivy, James H. Doroshow, Alice P. Chen
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor with few treatment options. We designed a phase II randomized trial to determine the activity and tolerability of single-agent cediranib or sunitinib in patients with advanced metastatic ASPS. Patients and Methods: Patients 16 years of age and older were randomized to receive cediranib (30 mg) or sunitinib (37.5 mg) in 28-day cycles. Patients could cross over to the other treatment arm at disease progression. The primary endpoint was to measure the objective response rate (ORR) for each agent. Median progression-free survival (mPFS) for the two arms was also determined. Results: Twenty-nine of 34 enrolled patients were evaluable for response. One patient on each of the initial two treatment arms had a partial response (ORR: 6.7% and 7.1% for cediranib and sunitinib, respectively). Twenty-four patients had a best response of stable disease (86.7% and 78.6% for cediranib and sunitinib, respectively). There were no significant differences in mPFS for the two treatment arms. Clinical benefit (i.e., objective response or stable disease for a minimum of four or six cycles of therapy) on the first-line tyrosine kinase inhibitor (TKI) therapy did not predict benefit on the second-line TKI. Both drugs were well tolerated. As of August 2021, 1 patient (unevaluable for ORR) remains on study. Conclusions: The study did not meet its endpoints for ORR. Although both TKIs provided clinical benefit, the outcomes may have been attenuated in patients who had progressed ≤6 months before enrollment, potentially accounting for the low response rates. See related commentary by Wilky and Maleddu, p. 1163
Diabetes-Related Excess Mortality in Mexico: A Comparative Analysis of National Death Registries Between 2017–2019 and 2020
Authors: Omar Yaxmehen Bello-Chavolla, Neftali Eduardo Antonio-Villa, Carlos A. Fermín-Martínez, Luisa Fernández-Chirino, Arsenio Vargas-Vázquez, Daniel Ramírez-García, Martín Roberto Basile-Alvarez, Ana Elena Hoyos-Lázaro, Rodrigo M. Carrillo-Larco, Deborah J. Wexler, Jennifer Manne-Goehler, Jacqueline A. Seiglie
Journal: Diabetes Care (2022)

To estimate diabetes-related mortality in Mexico in 2020 compared with 2017-2019 after the onset of the coronavirus disease 2019 (COVID-19) pandemic.This retrospective, state-level study used national death registries of Mexican adults aged ≥20 years for the 2017-2020 period. Diabetes-related death was defined using ICD-10 codes listing diabetes as the primary cause of death, excluding certificates with COVID-19 as the primary cause of death. Spatial and negative binomial regression models were used to characterize the geographic distribution and sociodemographic and epidemiologic correlates of diabetes-related excess mortality, estimated as increases in diabetes-related mortality in 2020 compared with average 2017-2019 rates.We identified 148,437 diabetes-related deaths in 2020 (177 per 100,000 inhabitants) vs. an average of 101,496 deaths in 2017-2019 (125 per 100,000 inhabitants). In-hospital diabetes-related deaths decreased by 17.8% in 2020 versus 2017-2019, whereas out-of-hospital deaths increased by 89.4%. Most deaths were attributable to type 2 diabetes (130 per 100,000 inhabitants). Compared with 2018-2019 data, hyperglycemic hyperosmolar state and diabetic ketoacidosis were the two contributing causes with the highest increase in mortality (128% and 116% increase, respectively). Diabetes-related excess mortality clustered in southern Mexico and was highest in states with higher social lag, rates of COVID-19 hospitalization, and prevalence of HbA1c ≥7.5%.Diabetes-related deaths increased among Mexican adults by 41.6% in 2020 after the onset of the COVID-19 pandemic, occurred disproportionately outside the hospital, and were largely attributable to type 2 diabetes and hyperglycemic emergencies. Disruptions in diabetes care and strained hospital capacity may have contributed to diabetes-related excess mortality in Mexico during 2020.
PSMA-PET Detection of Unusual Metastases in Castrate-Sensitive Prostate Carcinoma
Authors: Nathanial Harris, Mun Yee Tan, Michael Ng, David Blakey, Mario Guerrieri, Daryl Lim Joon, Eddie Lau, Farshad Foroudi, Alexander Armstrong, Michael Chao
Journal: Clinical Nuclear Medicine (2022)

Prostate cancer (PCa) is a multifaceted, heterogeneous disease (with 7 molecular subtypes), which can metastasize to common sites, such as bone, lymph nodes, liver, and lungs. However, with PSMA PET imaging, rare sites of metastasis are increasingly discovered. We report 5 cases of unusual metastases in patients with castrate-sensitive PCa: solitary right inguinal nodal metastasis, solitary abdominal wall metastasis, penile shaft metastases, solitary perineum metastasis, and pleural metastases. These cases further support the use of PSMA-PET imaging in PCa monitoring, with the ability to detect solitary, small volume, and rare sites of metastases, which may not be apparent on conventional imaging.
CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states
Authors: Kun Leng, Indigo V. L. Rose, Hyosung Kim, Wenlong Xia, Wilber Romero-Fernandez, Brendan Rooney, Mark Koontz, Emmy Li, Yan Ao, Shinong Wang, Mitchell Krawczyk, Julia TCW, Alison Goate, Ye Zhang, Erik M. Ullian, Michael V. Sofroniew, Stephen P. J. Fancy, Matthew S. Schrag, Ethan S. Lippmann, Martin Kampmann
Journal: Nature Neuroscience (2022)
Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial
Authors: Lucia Bailón, Anuska Llano, Samandhy Cedeño, Tuixent Escribà, Miriam Rosás-Umbert, Mariona Parera, Maria Casadellà, Miriam Lopez, Francisco Pérez, Bruna Oriol-Tordera, Marta Ruiz-Riol, Josep Coll, Felix Perez, Àngel Rivero, Anne R. Leselbaum, Ian McGowan, Devi Sengupta, Edmund G. Wee, Tomáš Hanke, Roger Paredes, Yovaninna Alarcón-Soto, Bonaventura Clotet, Marc Noguera-Julian, Christian Brander, Jose Molto, Beatriz Mothe, Ana María Barriocanal, Susana Benet, Patricia Cobarsi, Romas Geleziunas, Anne R. Leselbaum, Cora Loste, Michael Meulbroek, Cristina Miranda, Jose Muñoz, Jordi Naval, Aroa Nieto, Ferran Pujol, Jordi Puig
Journal: Nature Medicine (2022)